IGF::OT::IGF SBIR Topic 355: A 3D Perfusable Platform for HTS Across Diverse Racial/Ethnic Cancer Specimens To generate racially diverse patient-derived xenograft (PDX)-derived prostate cancer culture

在美国，非裔美国人罹患前列腺癌的几率是白人男性的两倍多。导致这种差异的潜在因素尚未在功能研究中得到证实，因为具有代表性的体外模型对研究界来说并不容易获得。这个问题有两个根源。首先，目前还不存在来自具有代表性的种族和民族背景的前列腺癌肿瘤细胞的多样化来源。第二，二维(2D)癌症药物筛选模型预测患者体内肿瘤反应的不准确是有效候选药物选择的主要障碍，也是导致癌症药物临床失败率高的原因之一。这增加了评估可能导致癌症健康差异(CHD)的潜在微妙生物因素的难度。在这项提案中，米米塔斯及其在莱斯大学的合作者将开发和展示由PDX衍生的白人、西班牙裔和非裔美国人的PCA培养的种族多样性群体的可行性 起源于Mimetas 3D OncoPlatform高通量平台，包含96个体外微肿瘤。我们的平台将通过整合共培养的基质细胞、细胞外基质(ECM)和持续灌流来模拟3D肿瘤微环境，以更好地预测患者的反应，并支持CHD研究。我们将进行相关疗法的药物筛选，以展示我们平台的重复性和预测能力。在一个潜在的第二阶段，我们将把培养模型的数量扩大到完全不同种族的集合，并开发转移和血管生成潜力的输出。

African-American men have the highest incidence of prostate cancer (PCa) are more than twice as likely to die than Caucasian men in the US. Underlying factors that cause this disparity have yet to be confirmed in functional studies as representative in vitro models are not readily available to the research community. This problem has two origins. First, a diverse source of PCa tumor cells from representative racial and ethnic backgrounds does not currently exist. Second, the inaccuracy of two-dimensional (2D) cancer drug screening models in predicting in vivo tumor responses in patients is a major hurdle for effective candidate drug selection and contributes to the high rate of cancer drug clinical failures. This compounds the difficulty of assessing potentially subtle biological factors that may contribute to cancer health disparities (CHD). In this proposal, Mimetas and its collaborators at Rice University will develop and demonstrate the feasibility of a racially diverse population of PDX derived PCa cultures of Caucasian, Hispanic, and African-American origin in Mimetas 3D OncoPlate high-throughput platform containing 96 ex vivo micro tumors. Our platform will mimic the 3D tumor microenvironment by integrating co-cultured stromal cells, extracellular matrix (ECM), and continuous perfusion, to will better predict patient responses, and support CHD research. We will perform a drug screen of relevant therapeutics to display the reproducibility and predictive ability of our platform. In a potential Phase II, we will expand the number of culture models to a fully racially diverse set and develop outputs for metastatic and angiogenesis potential.